Safety and Preliminary Efficacy of MBS8(1V270) in Cancer Patients With Advanced Solid Tumours

Exclusion Criteria

• •1. Have had biologic, hormonal, anti-neoplastic chemotherapy, or radiation therapy within 4 weeks prior to Screening (6 weeks required for nitrosourea or mitomycin) except for medications with half-lives \<5.5 days.
• •2. Metastatic disease that involved major airways or blood vessels or centrally located mediastinal tumour masses of large volume with close relation to the major airways, where tumour necrosis may have caused perforation or severe bleeding episodes. Primary or metastatic intestinal disease in situ where tumour necrosis may have caused gastrointestinal perforation.
• •3. Use of investigational agent in the 4 weeks or 5 half-lives prior to the first dose of MBS8(1V270), whichever was shortest.
• •4. Major surgical procedure within 14 days prior to the first dose of trial treatment.
• •5. Had a history of another primary malignancy, except for:
• •• Malignancy treated with curative intent and with no known active disease within 2 years prior to the first dose of MBS8(1V270)
• •• Adequately treated non-invasive basal skin cancer or squamous cell skin carcinoma
• •• Adequately treated uterine cervical cancer Stage 1B or less.
• •6. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids \[\>10 mg prednisone per day or equivalent, except topical or inhaled\] cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-IL-6 receptor agents, and anti-tumour necrosis factor \[TNF\]α agents) within 2 weeks prior to initiation of trial treatment, or anticipation of need for systemic immunosuppressive medication during trial treatment.
• •7. Treatment with androgen deprivation therapies such as luteinizing hormone-releasing hormone (LHRH) (gonadotropin-releasing hormone \[GnRH\]) agonists within 2 weeks prior to initiation of trial treatment.
• •8. Ongoing irAEs and/or AEs Grade ≥2 not resolved from previous therapies except vitiligo, resolved atopy, limited psoriasis, stable neuropathy Grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy.
• •9. Had uncontrolled intercurrent or chronic illness, but not limited to, ongoing or active infection such as hepatitis B or C, human immunodeficiency virus (HIV), immune dysfunction such as autoimmune disease, psychiatric illness such as depression or suicidal tendency or social situations that would have limited compliance with trial requirements.
• •10. Had active or history of immunologic-mediated disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, or Guillain-Barré syndrome.
• •11. Had clinically significant cardiac disease, including:
• •• Known congestive heart failure Grade III or IV by the New York Heart Failure Association (see Appendix A)
• •* Myocardial infarction within 6 months prior to signing the ICF
• •* Onset of unstable angina within 6 months prior to signing the ICF.
• •12. History of severe allergic episodes.
• •13. Known hypersensitivity to any component of MBS8(1V270).
• •14. Had a history of seizure disorders uncontrolled on medication.
• •15. Had a history of clinically significant coagulation or bleeding disorders or abnormalities.
• •16. Abnormal or clinically significant coagulation parameters (i.e., INR and APTT) at the discretion of the Investigator.
• •Participants treated with anticoagulants were excluded if the coagulation parameters were outside the therapeutic intervals as described in the SmPC for the administered treatment.
• •17. Women of childbearing potential who denied remaining abstinent (refrain from heterosexual intercourse) or did not use a highly effective form of contraception that resulted in a failure rate of \<1% per year during the Treatment period and up to 120 days after the last trial drug administration.
• •18. Men of reproductive potential who denied following accepted contraception methods during the Treatment and up to 120 days after the last trial drug administration.
• •19. Pregnant or lactating women.
• •20. Had a history or current evidence of any condition, therapy, or laboratory abnormality that might have confounded the results of the trial, interfered with the participant's participation for the full duration of the trial, made administration of the trial drugs hazardous, or made it difficult to monitor adverse effects such that it was not in the best interest of the participant to participate, and in the opinion of the treating Investigator.
• •21. Had an autoimmune disorder requiring immune-modulating treatment (\>10 mg prednisone per day or equivalent, except topical or inhaled) during the last 2 years prior to the first dose of MBS8(1V270).
• •1. Uncontrolled intercurrent illness: active infection requiring IV therapy, uncontrolled congestive heart failure, unstable angina, significant arrhythmia, recent myocardial infarction (≤6 months), or uncontrolled hypertension.
• •2. Known active HIV with uncontrolled viraemia, active hepatitis B virus (HBV)/hepatitis C virus (HCV) with high viral load (HBV \>20,000 IU/mL and HCV \>800,000 IU/mL) despite therapy (enrol per local guidelines, if controlled).
• •3. Pregnant or breastfeeding.
• •4. Second malignancy requiring active therapy (except adequately treated non-melanoma skin cancers, in situ cancers, or malignancies in remission ≥2 years)
• •5. Allergy/hypersensitivity to trial drug components.
• •6. Live vaccines within 28 days prior to C1D1.
• •7. QTcF \>500 ms.
• •8. Any condition that, in the Investigator's judgement, compromises safety or compliance.
• •9. Active autoimmune disease requiring systemic treatment in the past 2 years (topicals/inhaled/physiologic replacement allowed).
• •10. Any prior exposure to systemic or IT immunotherapy (except tebentafusp, pembrolizumab, nivolumab, ipilimumab, and relatlimab), but including Montanide, TLR7, TLR8, and TLR9 agonists, polyinosinic:polycytidylic acid, cationic adjuvant formulation, messenger ribonucleic acid -based vaccines, T cell therapy, and oncolytic viruses.
• •11. Participants who have been previously treated with experimental anti-cancer vaccines.
• •13A. Interstitial lung disease/pneumonitis (current or history requiring steroids).
• •14A. Concurrent anti-cancer therapy other than trial-allowed supportive care. 15A. Histologically/cytologically confirmed cutaneous acral melanoma and mucosal melanoma.
• •13B. Any contraindication specific to MBS8(1V270) per IB (e.g., known hypersensitivity to excipients, cohort-specific risk factors).
• •14B. Brain metastases.